Macrocycle-based drug design represents an exciting new frontier in drug discovery, and consequently there is considerable interest in methodologies for the efficient construction of macrocyclic motifs. However, typical high-dilution macrocyclization conditions are inefficient and impractical in a pharmaceutical setting from cost, capacity and green chemistry perspectives. This critical review reports the results of a comprehensive literature survey of recent macrocyclization reactions and proposes a macrocyclization efficiency index, Emac, which takes into account both reaction yield and concentration. Analysis and discussion of the literature dataset using this novel metric are presented, along with selected examples of high and low efficiency macrocyclizations.